Treatment and prophylaxis of cardiac allograft vasculopathy.
Cardiac allograft vasculopathy (CAV) remains a life-threatening complication after heart transplantation (HT). Recipients with severe intimal thickening are 10-fold more likely to suffer cardiac events than those without severe hyperplasia. From July 1987 to July 2007, we performed 323 HTs with 5-year actuarial freedom from CAV of 69%, similar to the data reported by the International Society for Heart and Lung Transplantation, namely, 68% at 5 years. Therefore, CAV is not uncommon in Asia. The pathogenesis of CAV is initial endothelial injury followed by intimal hyperplasia and proliferation of vascular smooth muscle cells. It may be caused by both immunological events (involving T or B cells in response to donor major histocompatibility antigens, or natural killer [NK] cell-triggered recruitment of T cells not responsive to donor alloantigen) and nonimmunologic factors, such as older age, ischemia-reperfusion injury, viral infection (particularly cytomegalovirus [CMV] infection), immunosuppressive drugs, and classic risk factors, such as hyperlipidemia, insulin resistance, and hypertension. The therapy for CAV has been disappointing, despite prescriptions of statin lipid-lowering agents, calcium-channel blockers, angiotensin-converting enzyme inhibitors, and antiproliferative drugs. Patients with CAV are often not amenable to successful revascularization (medical or surgical) because of the diffuse obliterative process. Prophylaxis of CAV starts with modification of risk factors: hypertension, hyperlipemia, hyperglycemia, obesity, and smoking, as well as promotion of exercise programs. The HMG-CoA reductase inhibitors and antiproliferative drugs may slow the progression of CAV by various immunologic and nonimmunologic effects. Prevention of CMV infection reduces CAV. Mycophenolate mofetil and signal transduction inhibitors, such as everolimus, reduce intimal thickening and CAV.
Wang
S-S
SS
Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan.
D001402:B-Lymphocytes / Q000276:immunology; D016027:Heart Transplantation / Q000276:immunology / Q000473:pathology*; D006801:Humans; D008285:Major Histocompatibility Complex; D011183:Postoperative Complications / Q000517:prevention & control*; D013601:T-Lymphocytes / Q000276:immunology; D014184:Transplantation, Homologous / Q000276:immunology / Q000473:pathology*; D017539:Tunica Intima / Q000276:immunology / Q000473:pathology; D014652:Vascular Diseases / Q000517:prevention & control*